ESPE Abstracts

Background: Hypophosphatemic rickets (HR) associated with elevated FGF23 plasma levels is a disorder characterized by renal phosphate wasting, leading to impaired bone mineralization. Conventional therapy, based on oral phosphate and calcitriol, has limited efficacy and tolerability. In 2018, burosumab, a monoclonal antibody against fibroblast growth factor 23 (FGF-23), was approved for the treatment of X-linked hypophosphatemia (XLH). However, data on burosumab’s effect on growth in children with XLH remain limited.

Methods: We conducted a single-center retrospective study on six children with HR, of which five with PHEX mutations and one with an HRAS mutation (mean age 12 years, 3 females and 3 males). Patients shifted from conventional oral treatment to Burosumab, with a follow-up period ranging from 8 months to 3 years. Growth velocity, standing height and sitting height (SH/H ratio) were evaluated using Cacciari Italian reference curves for standing height and Fredriks Dutch reference charts for trunk and limb measurements.

Results: All our patients started conventional therapy within the first two years of life maintaining a good compliance, and received early interventions for varus knees through physiatric treatment (braces). Only one underwent epiphysiodesis. Although a growth velocity below the general population for age and sex was evident for most of our patients, they showed constant and harmonic linear growth during the pre-pubertal years. Linear growth and body proportions during conventional therapy were positively influenced by early initiation of physiatric interventions. During puberty, in contrast, there was a greater increase in trunk growth compared to limb growth, leading to an increased SH/H ratio over time. Despite the small sample size precluding statistical analysis, most patients showed improved growth velocity after burosumab initiation. No changes in trunk and limb growth velocities were observed after the therapy switch, maintaining a stable SH/H ratio.

Discussion: Longitudinal growth of long bones is significantly impacted in patients with bone dysplasia and limb bowing can affect height measurements, leading to disharmonic growth with differing growth rates between the trunk and limbs. While burosumab's efficacy in improving calcium-phosphate metabolism in XLH patients is evident, its positive effect on growth remains unclear. To better monitor prepubertal and pubertal growth in HR patients in burosumab, it is important to use appropriate auxological tools, including sitting height evaluation (SH/H ratio).